High priority will be given to continuing investigations of biochemical aspects of the mosquito-filaria relationship, using Brugia pahangi-infected Aedes aegypti as a model. Of immediate concern is whether the observed increased dihydrofolate reductase activity in extracts of female mosquitoes with advanced filarial infection is due to adulteration of the extracts with the analogous filarial enzyme or whether it represents a true response of the arthropod host to infection. Three new active schistosomicidal and/or macrofilaricidal agents have been identified in our in vitro screening systems. Mechanistic studies of these compounds are in progress. Two of these compounds, thiocyanatouridine derivatives, are the first pyrimidine analogs shown to possess anthelmintic activity. There will be continuing attempts to improve the therapeutic index of the antischistosomal drug tubercidin, administered by direct intravenous injection. The approach to be followed, pioneered by workers in cancer chemotherapy, involves trying to modify the potential renal toxicity of our drug by prior fluid loading of the experimental subject and induction of osmotic diuresis with mannitol while tubercidin is being infused. BIBLIOGRAPHIC REFERENCES: Voge, M., J.J. Jaffe, D.A. Bruckner, and E. Meymarian. 1976. Synergistic growth promoting action of L-cysteine and nitrogen upon Hymenolepis diminuta cysticercoids in vitro. J. Parasitol. 62: in press. Jaffe, J.J., H.M. Doremus, and E. Meymarian. 1976. Activity of tubercidin against immature Fasciola hepatica in mice. J. Parasitol: in press.